一种微乳液用于口服输送的Nintedanib - QbD启用配方开发,体外表征和体外药物动力学评估
Dnyandev Gadhave1, Mural Quadros1, Mimansa Goyal1
1Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, New York, 11439, USA.
The AAPS journal
|August 11, 2025
概括
这项研究开发了一种新型的Nintedanib装载微乳液 (Nint-ME),用于改善异常性肺纤维化 (IPF) 治疗的口服输送. 优化的Nint-ME配方显著增强了Nintedanib的功效.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 纳米技术纳米技术
背景情况:
- 宁达尼布 (Nint) 对于异形性肺纤维化 (IPF) 是至关重要的,但具有较差的溶解性和较低的口服生物利用性 (<5%).
- 现有的Nintedanib输送方法由于其快速代谢降解而面临挑战.
- 克服这些局限性对于在IPF患者中有效的Nintedanib治疗至关重要.
研究的目的:
- 制定和优化一个含有Nintedanib的微乳液 (Nint-ME) 以提高口服输送.
- 评估Nint-ME.的物理化学性质,体外释放和体内药物动力学特征.
- 评估Nint-ME在克服Nintedanib的输送限制方面的治疗潜力.
主要方法:
- 使用低能量的油在水 (O/W) 乳化和水滴定来制备Nint-ME,通过设计质量 (QbD) 方法进行优化.
- 描述包括球体大小,PDI,封装效率,透射率,表面电荷和粘度.
- 进行了体外释放动力学,Caco-2细胞透性和体内药理动力学研究.
主要成果:
- 优化的Nint-ME表现出了理想的特征:23.8 nm球体大小,0.18 PDI,99.8%的封装效率和-0.7 mV的表面电荷.
- 在72小时内释放高的宁达尼布 (94.5%) 随着第一阶段动力学,表明控制释放.
- 试验室研究显示了显著的Caco-2细胞透,而体内研究显示,与Nintedanib悬浮相比,口服生物利用率增加了2倍.
结论:
- 成功开发了一种口服中含有Nintedanib的微乳液 (Nint-ME) 配方.
- Nint-ME证明了Nintedanib. 的可溶性,稳定性得到改善,并且口服生物可用性显著提高.
- 这种新的配方为IPF治疗中安全有效的Nintedanib输送提供了有前途的战略.
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